Project Summary/Abstract Early childhood, from birth to age 6 years, is a period of very rapid expansion of the basic structural and functional framework of the brain. Schizophrenia is a complex and serious mental disorder with neurodevelopmental origins. However, it remains unclear how genetic and environmental influences contribute to individual differences seen during the very early stages of neurodevelopment. The identification of early developmental precursors can bring a greater understanding of the fundamental neurobiology involved in the advancement of this disorder. To aid in bridging this gap we will conduct, to our knowledge, the first study that seeks to determine the relationship between inherited risk for schizophrenia and brain structure and cognitive development. We hypothesize that alterations in brain structure and cognition will be associated with risk for schizophrenia. Our unique subject population (N=669) consists of infants with a maternal history of schizophrenia/schizoaffective disorder (N=107), twin pairs (N=303), and typically developing controls (N=289). We aim to 1.) Determine the relationship between cognition and brain structure development and having an inherited risk for schizophrenia using structural Magnetic Resonance Imaging (sMRI) and the Mullen Scales of Early Learning, 2.) Determine the relationship between being at risk for schizophrenia and having increased extra-axial CSF (EAF) utilizing our unique computer-assisted imaging pipeline for the quantification of EAF in the developing brain, and 3.) Determine the genetic and environmental contributions to the development of EAF using twin pairs and heritability analyses. Identifying possible risk markers that are related to the disruption of neurodevelopment and involved in the progression of schizophrenia can provide advancements in preventative interventions and treatments, prior to the onset of psychotic symptoms.